This program represents a broadly based study of several aspects of lymphocyte biology with particular emphasis on the cellular basis of the immune response mechanism and its involvement in neoplastic states. Specifically, the projects deal with: (1) Interactions of T- lymphocytes with histocompatibility (H) antigens in the mixed-lymphocyte interaction (MLI) and graft-versus-host (GVH) reaction: the preparation and characterization of antigen-selected populations of T-lymphocytes; involvement of T-lymphocytes in immuno-surveillance and immune- stimulation of tumors; and inter-relationships between memory and effector T-lymphocytes. (2) Mechanisms of B-lymphocyte stimulation and tolerance induction; the clonal response of B-cells to tumor and to defined antigen systems; and physiological factors regulating levels of antibody production by cloned B-cells. (3) The biology and specificity of T-cells in helper function. (4) The genetics of H-antigens and involvement of these polymorphisms in immuno-surveillance; immune responses to enzymatically treated allogeneic cells; the maintenance of tolerance to H-antigens; and biology of tumors maintained in immunologicaly privileged sites. (5) Genetic control of immuno- surveillance mechanisms as related to experimental leukemia. (6) Surface characteristics of normal and neoplastic human lymphocytes. This program is a component of the proposed University of Pennysylvania Cancer Center.